Sortin1-hypersensitive mutants link vacuolar-trafficking defects and flavonoid metabolism in Arabidopsis vegetative tissues

Sortin1 is a chemical genetic-hit molecule that causes specific mislocalization of plant and yeast-soluble and membrane vacuolar markers. To better understand its mode of action, we designed a Sortin1-hypersensitive screen and identified several Sortin1-hypersensitive and flavonoid-defective mutants. Mechanistically, Sortin1 mimics the effect of the glutathione inhibitor buthionine sulfoximine and alters the vacuolar accumulation of flavonoids, likely blocking their transport through vacuole-localized ABC transporters. Structure-activity relationship studies conducted in Arabidopsis revealed the structural requirements for Sortin1 bioactivity and demonstrated that overlapping Sortin1 substructures can be used to discriminate between vacuolar-flavonoid accumulations and vacuolar-biogenesis defects. We conclude that Sortin1 is a valuable probe for dissecting novel links among flavonoid transport, vacuolar integrity, and the trafficking of vacuolar targeted cargoes in Arabidopsis.     

In vitro anti-HMPV activity of meroditerpenoids from marine alga Stypopodium zonale (Dictyotales)

In this paper, we evaluated the antiviral activity against HMPV replication of crude extract of the marine algae Stypopodium zonale and of two meroditerpenoids obtained from it, atomaric acid and epitaondiol, and a methyl ester derivative of atomaric acid. Their selectivity indexes were 20.78, >56.81, 49.26 and 12.82, respectively. Compared to ribavirin, the substances showed a relatively low cytotoxicity on LLC-MK2 cells, with a significant antiviral activity, inhibiting at least 90% of viral replication in vitro, which demonstrates the potential of these marine natural products to combat infections caused by HMPV in vitro.     

Metal-mediated aggregation of DNA comprising 2,2'-bipyridine nucleoside, an asymmetrically substituted chiral bidentate ligand

The incorporation of an artificial 5-methyl-2,2'-bipyridine nucleoside at the 5' terminus of an otherwise self-complementary oligonucleotide sequence opens up the opportunity of metal-mediated aggregation of DNA double helices triggered by the addition of the respective metal ions. Interestingly, two-dimensional aggregates (DNA monolayers) are formed in the presence of nickel(ii), whereas copper(ii) leads to the formation of three-dimensional disc-shaped structures. With iron(ii), a coexistence of both types of aggregates had been observed previously. Models are proposed in which these observations are explained based on geometrical considerations. The artificial nucleoside itself represents a rare example for a C(1)-symmetric chiral derivative of 2,2'-bipyridine, enabling the formation of four isomeric octahedral complexes.     

Promising anticancer mono- and dinuclear ruthenium(III) dithiocarbamato complexes: systematic solution studies

During the last decade, our research group has prepared a number of metal dithiocarbamato derivatives of Pt, Pd and Au that were expected to resemble the main features of cisplatin together with higher activity, improved selectivity and bioavailability, and lower side-effects. Furthermore, we have already published the synthesis, characterization and in vitro cytotoxicity studies of novel ruthenium(III) dithiocarbamato complexes such as [RuL(3)] monomers (11) and α-[Ru(2)L(5)]Cl dimers (12) with five different dithiocarbamate ligands. As both the monomer and the dinuclear complexes have shown significant antitumor activity in different human tumor cell lines, we decided to widen the characterization studies and to analyse thoroughly their behavior in physiological-like medium by UV-visible and CD spectroscopy. In the present paper we report on the crystal structure of [Ru(DMDT)(3)], [Ru(PDT)(3)] and [Ru(ESDT)(3)] complexes and we determine the spin state of the paramagnetic Ru(III) by means of Evans' method. Then, we discuss in detail the UV-visible spectral data of the complexes in different medium. All the studied complexes are stable in dimethyl sulfoxide, and show low solubility in phosphate buffered saline solution, particularly the monomer species, even at low concentration, while increased solubility for both types of complexes have been found in the presence of bovine serum albumin (BSA). Moreover, no changes on the coordination sphere of the metal, as well as no direct interaction between the BSA protein and the complex have been identified by UV-visible spectroscopy. However, some conformational changes on the BSA structure, induced by the ruthenium(III) complexes have been confirmed by CD spectroscopy, indicating a probable secondary electrostatic interaction between the metal complex and the peptide. In addition, no significant interaction has been demonstrated with the components of Dulbecco's Modified Eagle's Medium, used for the in vitro assays.     

On a wave equation with supercritical interior and boundary sources and damping terms

This article addresses nonlinear wave equations with supercritical interior and boundary sources, and subject to interior and boundary damping. The presence of a nonlinear boundary source alone is known to pose a significant difficulty since the linear Neumann problem for the wave equation is not, in general, well‐posed in the finite‐energy space H¹(Ω) × L₂(?Ω) with boundary data in L₂ due to the failure of the uniform Lopatinskii condition. Further challenges stem from the fact that both sources are non‐dissipative and are not locally Lipschitz operators from H¹(Ω) into L₂(Ω), or L₂(?Ω). With some restrictions on the parameters in the model and with careful analysis involving the Nehari Manifold, we obtain global existence of a unique weak solution, and establish exponential and algebraic uniform decay rates of the finite energy (depending on the behavior of the dissipation terms). Moreover, we prove a blow up result for weak solutions with nonnegative initial energy.     

Assessment of the In Vivo Release and Biocompatibility of Novel Vesicles Containing Zinc in Rats

This paper is focused on the in vivo release and biocompatibility evaluation in rats of some novel systems entrapping zinc chloride in lipid vesicles. The particles were prepared by zinc chloride immobilization inside lipid vesicles made using phosphatidylcholine, stabilized with 0.5% chitosan solution, and dialyzed for 10 h to achieve a neutral pH. The submicrometric systems were physico-chemically characterized. White Wistar rats, assigned into four groups of six animals each, were treated orally with a single dose, as follows: Group I (control): deionized water 0.3 mL/100 g body weight; Group II (Zn): 2 mg/kg body weight (kbw) zinc chloride; Group III (LV-Zn): 2 mg/kbw zinc chloride in vesicles; Group IV (LVC-Zn): 2 mg/kbw zinc chloride in vesicles stabilized with chitosan. Haematological, biochemical, and immune parameters were assessed after 24 h and 7 days, and then liver fragments were collected for histopathological examination. The use of zinc submicrometric particles—especially those stabilized with chitosan—showed a delayed zinc release in rats. No substantial changes to blood parameters, plasma biochemical tests, serum complement activity, or peripheral neutrophils phagocytic capacity were noted; moreover, the tested substances did not induce liver architectural disturbances. The obtained systems provided a delayed release of zinc, and showed good biocompatibility in rats.     

Description and interpretation of the bracts epidermis of Gramineae (Poaceae) with rotated image with maximum average power spectrum (RIMAPS) technique

During the last few years, RIMAPS technique has been used to characterize the micro-relief of metallic surfaces and recently also applied to biological surfaces. RIMAPS is an image analysis technique which uses the rotation of an image and calculates its average power spectrum. Here, it is presented as a tool for describing the morphology of the trichodium net found in some grasses, which is developed on the epidermal cells of the lemma. Three different species of grasses (herbarium samples) are analyzed: Podagrostis aequivalvis (Trin.) Scribn. & Merr., Bromidium hygrometricum (Nees) Nees & Meyen and Bromidium ramboi (Parodi) Rúgolo. Simple schemes representing the real microstructure of the lemma are proposed and studied. RIMAPS spectra of both the schemes and the real microstructures are compared. These results allow inferring how similar the proposed geometrical schemes are to the real microstructures. Each geometrical pattern could be used as a reference for classifying other species. Finally, this kind of analysis is used to determine the morphology of the trichodium net of Agrostis breviculmis Hitchc. As the dried sample had shrunk and the microstructure was not clear, two kinds of morphology are proposed for the trichodium net of Agrostis L., one elliptical and the other rectilinear, the former being the most suitable.     

Determination of cocaine adulterants in human urine by dispersive liquid-liquid microextraction and high-performance liquid chromatography

Analytical and Bioanalytical Chemistry - This study aimed to determine simultaneously five major street cocaine adulterants (caffeine, lidocaine, phenacetin, diltiazem, and hydroxyzine) in human...     

Generalized gradient approximation adjusted to transition metals properties: Key roles of exchange and local spin density

Perdew-Burke-Ernzerhof (PBE) and PBE adapted for solids (PBEsol) are exchange-correlation (xc) functionals widely used in density functional theory simulations. Their differences are the exchange, μ, and correlation, β, coefficients, causing PBEsol to lose the Local Spin Density (LSD) response. Here, the μ/β two-dimensional (2D) accuracy landscape is analyzed between PBE and PBEsol xc functional limits for 27 transition metal (TM) bulks, as well as for 81 TM surfaces. Several properties are analyzed, including the shortest interatomic distances, cohesive energies, and bulk moduli for TM bulks, and surface relaxation degree, surface energies, and work functions for TM surfaces. The exploration, comparing the accuracy degree with respect experimental values, reveals that the found xc minimum, called VV, being a PBE variant, represents an improvement of 5% in mean absolute percentage error terms, whereas this improvement reaches ~11% for VVsol, a xc resulting from the restoration of LSD response in PBEsol, and so regarded as its variant.     

Highly shifted LIPOCEST agents based on the encapsulation of neutral polynuclear paramagnetic shift reagents

Improved LIPOCEST MRI contrast agents with highly shifted intraliposomal water protons were prepared by entrapping neutral polynuclear Tm(III)-based paramagnetic shift reagents in phospholipidic vesicles.